The syndrome of medullary carcinoma of the thyroid, pheochromocytoma and parathyroid gland hyperplasia or Multiple Endocrine Neoplasia Syndrome-Type II, is transmitted as an autosomal dominant trait with an approximate 50% chance of occurrence in children of an affected parent. In a large New Haven kindred, comprising more than 120 members living in a close proximity to New Haven, annual screening of individuals 4 years of age and older has been performed for the past 4 years in the ambulatory facilities of the Adult (General) and Children's Clinical Research Centers, Yale-New Haven Medical Center. To December 1979, pentagastrin provocation, 0.5 mcg/kg and measurement of calcitonin by immunoassay was used as the screening procedure for medullary carcinoma. Positive responses were seen only in individuals previously known to have disease. As of 12/1/79 the procedure was altered to use a combined pentagastrin-calcium infusion based on the above recent data. Screening for parathyroid disease is performed simultaneously with the infusion using total and ionized calcium, alkaline phosphatase and immunoreactive parathormone levels. Urinary catecholamines are obtained on 24 hours collections and assayed in the laboratory of Dr. Lewis Landsberg, Beth Israel Hospital, for pre-symptomatic detection of pheochromocytoma. Genetic analysis of the kindred performed during the year has succeeded in identifyiing one of the four main branches of the kindred as almost certainly not at risk based on absence of the disease through 4 generations and normal testing via pentagastrin provocation in more senior members of the branch. It is hoped that further analysis of the family pedigree using the clinical histories and responses to provocation will serve to eliminate other members of the family from active follow-up as "at risk" for MEN Type II.